title: How metabolism generates signals during innate immunity and inflammation.
abstract: The interplay between immunity, inflammation, and metabolic changes is a growing field of research. Toll-like receptors and NOD-like receptors are families of innate immune receptors, and their role in the human immune response is well documented. Exciting new evidence is emerging with regard to their role in the regulation of metabolism and the activation of inflammatory pathways during the progression of metabolic disorders such as type 2 diabetes and atherosclerosis. The proinflammatory cytokine IL-1β appears to play a central role in these disorders. There is also evidence that metabolites such as NAD(+) (acting via deacetylases such as SIRT1 and SIRT2) and succinate (which regulates hypoxia-inducible factor 1α) are signals that regulate innate immunity. In addition, the extracellular overproduction of metabolites such as uric acid and cholesterol crystals acts as a signal sensed by NLRP3, leading to the production of IL-1β. These observations cast new light on the role of metabolism during host defense and inflammation.
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Anne F
authors.initials: AF
authors.lastname: McGettrick
authors.forename: Luke A J
authors.initials: LA
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000502:physiology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D056564:Sirtuin 1 / Q000276:immunology / Q000378:metabolism; D056565:Sirtuin 2 / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C508585:IL1B protein, human; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D051193:Toll-Like Receptors; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2
keywords: Inflammation; Innate Immunity; Metabolic Diseases; Metabolic Regulation; Metabolism; Signal Transduction